Reproductive Experience Mitigates Cognitive Aging in a Mouse Model of Alzheimer's Disease

Reproductive Experience Mitigates Cognitive Aging in a Mouse Model of Alzheimer's Disease

Alvin Sherman Library

Alzheimer's disease (AD) is a devastating neurodegenerative disorder that lacks effective treatment. Despite women having approximately twice the risk for developing AD, few studies have investigated sex-specific factors contributing to disease vulnerability. Among women, motherhood appears to be protective, although results are mixed, and this relationship could be explained by a third variable (e.g., genes) influencing both disease risk and fertility or fecundity. During an experiment directly tested the effects of motherhood by manipulating access to male breeders and examining neurodegeneration and cognitive aging in control (B6129) and transgenic mice used to model AD (3xTg-AD mice), we also compared reproductive outcomes between strains to determine whether the human genes conferring AD risk alter fertility or fecundity. Female mice from each strain were paired with males through their first litter and postpartum estrus (when they could potentially be impregnated again to increase their reproductive output), and we assessed various measures of fecundity in two strains. Results suggest modest effects of AD-related genes on reproduction, with a general reduction in fecundity indicated. Specifically, 3xTg-AD mice had larger second litters than first litters, an effect absent in control females. Additionally, there was a main effect of strain, such that 3xTg-AD mice had smaller litter sizes across litters. Main effects of strain and litter, as well as strain x litter interactions, were observed for the number of male and female offspring. Together, these findings suggest that AD-related genetic risk modestly reduces fecundity. Although modest, it may be important to consider that part of the relationship between parity and dementia could be explained by genetics.